ROLE OF OESTROGENS AND GONADOTROPHINS IN PERPHENAZINE-INDUCED MAMMOGENESIS

Treatment of intact or recently (1 day) ovariectomized female rats with 5 mg perphenazine (Trilafon)/kg/day for 5 days resulted in marked lobulo\p=m-\ alveolar differentiation of the mammary glands. Perphenazine failed to stimulate mammogenesis in chronically (12 days) ovariectomized rats, unless they had been primed with oestradiol. However, mammogenic effects in chronically ovariectomized rats were obtained after implantation of minute amounts (2 \g=m\g)of oestradiol into the median eminence, or after treatment for 16 days with the non-steroid pituitary gonadotrophin-inhibitor methalli-bure (ICI 33828; 20 mg/kg/day). Since these latter procedures counteract the gonadotrophin surge after ovariectomy, it would appear that inhibition of gonadotrophin secretion is necessary before prolactin secretion can be stimulated by perphenazine. Castrated male rats responded to perphenazine with lobulo\p=m-\alveolar differentiation similar to that in intact males. The implications of this difference with regard to the mechanism of pituitary response to gonadec-tomy are discussed